Chromosome 3 has 7% of the human genome and is approximately 210 megabases. The construction of integrated physical and genetic maps for this chromosome, based on a common set of DNA markers, will be a powerful tool for studying the genetics of man. A consortium of 5 laboratories all with excellent resources for chromosome 3 has been formed to develop a 10 cM map of highly polymorphic markers for chromosome 3. To date there have been only a limited number of highly polymorphic markers developed for this chromosome. Four of the laboratories will isolate highly polymorphic markers from cosmids, YACs, and flow sorted libraries as well as minilibraries for specific regions of the chromosome. Polymorphisms will be predominantly based on (CA)n repeats which will be regionally localized on a physical map. The polymorphisms will be detected by a PCR based assay from sequence information flanking the (CA)n repeats. In addition, well established loci that are only slightly or moderately polymorphic will be analyzed for single stranded conformational polymorphisms and gradient gel electrophoresis to increase the level of polymorphism detected. These reagents will be typed in CEPH and Venezuelan families and the data will be analyzed to produce a genetic map. By two years we will generate a 10 cM map of markers that have a heterozygosity of 0.7 or greater. In the third year we will expand the map and fill in gaps towards the 2-5 cM map that is the 5 year goal of the Genome Project. The development of a genetic linkage map of human chromosome 3 will significantly facilitate the identification of disease genes in germline and malignant disorders. A set of markers that have been placed on both physical and genetic maps and are based on sequence will greatly accelerate the progress of mapping chromosome 3.